This invention relates to 12,13-oxo derivatives of 16 membered macrolides, e.g., tylosin and 23-demycinosyltylosin, pharmaceutical compositions containing them and methods of treating susceptible bacterial infections using such pharmaceutical compositions.
Sixteen membered macrolide antibiotics containing dienone chromophores are well known in the art. Tylosin is a naturally occurring macrolide antibiotic disclosed in U.S. Pat. No. 3,178,341. Other related macrolides are disclosed in U.S. Pat. No. 4,341,770 (5-O-mycaminosyltylonolide) (OMT), U.S. Pat. No. 4,321,361 (demycinosyltylosin) (DMT), U.S. Pat. No. 4,321,362 (demycinosyloxytylosin) (DMOT), U.S. Pat. No. 4,334,019 (demycinosyloxytylosin) and U.S. Pat. No. 4,443,436 (C-20 derivatives of tylosin, desmycosin, macrocin and lactenocin).
Numerous other sixteen-membered macrolide antibiotics appear in the article entitled "Macrolides" in Kirk-Othmer, Encyclopedia of Chemical Technology, third edition, vol. 2 p. 937 et sec. (1978).
Naturally occuring 16 membered epoxyenone or oxoenone macrolide antibiotics are well known. Rosaramicin is a 16 membered 12,13-oxoenone macrolide isolated from fermentation of Micromonospora rosaria (see U.S. Pat. No. 4,161,523). Mycinamicin I and II are other naturally occuring macrolides disclosed in U.S. Pat. No. 4,307,085. Various 12,13-epoxy derivatives of mycaminosyltylonide derivatives are disclosed in U.S. Pat. No. 4,454,314. See also U.S. Pat. No. 4,477,443 wherein 12,13-oxomycaminosyltylonolide, and the 4'-deoxy and 23-deoxy-23-dimethylamino derivatives are disclosed.
H. Tanaba, et al. (Paper 1150, 23th ICAAC, Minneapolis, Minn., Sept. 29, 1985) disclosed isolation of a naturally occurring 12,13-oxo-23-demycinosyloxytylosin, identified as M-119-a.
It would be desirable to have 16-membered oxoenone macrolides which exhibit enhanced antibacterial activity and high serum levels compared to those of other macrolides such as for example erythromycin, rosaramicin, and tylosin.